The characteristics of proteins and enzymes in living systems derive not only from structural genes, but also from the expression of accessory genetic elements. Included among these elements are the regulatory genes of bacteria and the genes required for the attachment of tail fibers to bacterial viruses. Although clearly documented analogies are lacking in animal systems, genetic elements have been described in Drosophila, in mice and in man which appear to control the subcellular location, developmental accumulation, hormonal responsiveness, rate of synthesis and rat of degradation of specific enzymes. The principal objective of the proposed research is to gain an understanding of genetic control mechanisms which underly the expression of enzymes and proteins in mammalian cells. This objective will be pursued by genetic and biochemical analyses of known mutations in mice which alter the expression of beta-glucuronidase and by identifying and analyzing mutations affecting secretory products of the mammary gland in mice.